Structural basis for mRNA recognition by human RBM38

Biochem J. 2020 Jan 17;477(1):161-172. doi: 10.1042/BCJ20190652.

Abstract

RNA-binding protein RBM38 was reported to bind the mRNA of several p53-related genes through its RRM domain and to up-regulate or down-regulate protein translation by increasing mRNA stability or recruitment of other effector proteins. The recognition mechanism, however, for RNA-binding of RBM38 remains unclear. Here, we report the crystal structure of the RRM domain of human RBM38 in complex with a single-stranded RNA. Our structural and biological results revealed that RBM38 recognizes G(U/C/A)GUG sequence single-stranded RNA in a sequence-specific and structure-specific manner. Two phenylalanine stacked with bases of RNA were crucial for RNA binding, and a series of hydrogen bonds between the base atoms of RNA and main-chain or side-chain atoms of RBM38 determine the sequence-specific recognition. Our results revealed the RNA-recognition mechanism of human RBM38 and provided structural information for understanding the RNA-binding property of RBM38.

Keywords: RBM38; RNA; RNA-binding proteins; crystallography; translational regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Humans
  • Protein Binding
  • Protein Domains
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins / chemistry*
  • RNA-Binding Proteins / metabolism*

Substances

  • RBM38 protein, human
  • RNA, Messenger
  • RNA-Binding Proteins